Aktas, BuseAkyuz, MesutKalayci, Sila EktasKara, Adem2026-03-262026-03-2620250250-46851303-829X10.1515/tjb-2025-0211https://doi.org/10.1515/tjb-2025-0211https://hdl.handle.net/20.500.14901/2927, Buse Aktaş/0009-0005-7024-7337; Akyüz, Mesut/0000-0001-8161-2479Objectives Head and neck squamous cell carcinoma (HNSCC) remain a major clinical challenge, with limited efficacy of current therapeutic regimens. Natural compounds such as oleuropein and pharmacological agents like atorvastatin have shown anticancer potential individually, yet their combined effects in HNSCC remain unexplored. This study aimed to evaluate the cytotoxic, antimigratory, and molecular effects of atorvastatin and oleuropein, alone and in combination, in FaDu pharyngeal carcinoma cells.Methods FaDu cells were treated with oleuropein, atorvastatin, or their combination. Cell viability was assessed by cell viability detection kit-8 (CVDK-8), migration by wound healing assay, and mRNA expression of apoptosis, proliferation, and signaling-related genes by real-time PCR.Results Oleuropein significantly reduced cell viability, induced BAX and PTEN expression, and suppressed CDK2 and CDK4, consistent with apoptosis induction and cell-cycle arrest. Atorvastatin alone exhibited minimal cytotoxicity but downregulated AKT and mTOR. Combination treatment attenuated oleuropein's cytotoxicity and increased BCL-2 expression, suggesting a potential antagonistic interaction. Neither atorvastatin nor its combination with oleuropein significantly inhibited cell migration.Conclusions This is the first study to investigate atorvastatin and oleuropein co-treatment in HNSCC cells. While oleuropein alone demonstrated potent anticancer effects, atorvastatin partially counteracted these activities, highlighting the complexity of drug-natural product interactions. Future studies should expand dose-response analyses, validate protein level mechanisms, and test in vivo models to clarify the translational potential of this novel combination.eninfo:eu-repo/semantics/openAccessHead and Neck CancerAtorvastatinOleuropeinApoptosisCombination TherapyCytotoxicityArticle